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Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era.
Kallianpur AR, Wang Q, Jia P, Hulgan T, Zhao Z, Letendre SL, Ellis RJ, Heaton RK, Franklin DR, Barnholtz-Sloan J, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Grant I, CHARTER Study Group
(2016) J Infect Dis 213: 1065-73
MeSH Terms: AIDS Dementia Complex, Adult, Anemia, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Cohort Studies, Cross-Sectional Studies, Erythrocyte Count, Erythrocyte Indices, Female, HIV Infections, Humans, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Predictive Value of Tests, Risk Factors
Show Abstract · Added December 11, 2019
BACKGROUND - Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown.
METHODS - We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments.
RESULTS - HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01).
CONCLUSIONS - Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.
© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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MeSH Terms
In vivo testing for gold nanoparticle toxicity.
Simpson CA, Huffman BJ, Cliffel DE
(2013) Methods Mol Biol 1026: 175-86
MeSH Terms: Animals, Blood Chemical Analysis, Blood Specimen Collection, Erythrocyte Count, Female, Gold, Leukocyte Count, Metal Nanoparticles, Mice, Mice, Inbred BALB C, Polyethylene Glycols, Species Specificity, Tissue and Organ Harvesting, Toxicity Tests, Urinalysis, Urine Specimen Collection
Show Abstract · Added January 20, 2015
A technique for measuring the toxicity of nanomaterials using a murine model is described. Blood samples are collected via submandibular bleeding while urine samples are collected on cellophane sheets. Both biosamples are then analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES) for nanotoxicity. Blood samples are further tested for immunological response using a standard Coulter counter. The major organs of interest for filtration are also digested and analyzed via ICP-OES, producing useful information regarding target specificity of the nanomaterial of interest. Collection of the biosamples and analysis afterward is detailed, and the operation of the technique is described and illustrated by analysis of the nanotoxicity of an injection of a modified tiopronin monolayer-protected cluster.
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16 MeSH Terms
Genetic variants that confer resistance to malaria are associated with red blood cell traits in African-Americans: an electronic medical record-based genome-wide association study.
Ding K, de Andrade M, Manolio TA, Crawford DC, Rasmussen-Torvik LJ, Ritchie MD, Denny JC, Masys DR, Jouni H, Pachecho JA, Kho AN, Roden DM, Chisholm R, Kullo IJ
(2013) G3 (Bethesda) 3: 1061-8
MeSH Terms: African Americans, Disease Resistance, Electronic Health Records, Erythrocyte Count, Erythrocyte Indices, Erythrocytes, Genome-Wide Association Study, Hematocrit, Hemoglobins, Humans, Malaria
Show Abstract · Added March 7, 2014
To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria-HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)-were associated (P ≤ 1 × 10(-6)) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 5 × 10(-8)) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans.
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11 MeSH Terms
In vivo toxicity, biodistribution, and clearance of glutathione-coated gold nanoparticles.
Simpson CA, Salleng KJ, Cliffel DE, Feldheim DL
(2013) Nanomedicine 9: 257-63
MeSH Terms: Animals, Erythrocyte Count, Glutathione, Gold, Kidney, Leukocyte Count, Mice, Mice, Inbred BALB C, Nanoparticles
Show Abstract · Added January 20, 2015
UNLABELLED - Gold nanoparticles are emerging as promising materials from which to construct nanoscale therapeutics and therapeutic delivery systems. However, animal studies have shown that gold nanoparticles modified with certain thiol monolayers such as tiopronin can cause renal complications and morbidity. Although these effects may be eliminated by coadsorbing small amounts of polyethylene glycol (PEG) onto the nanoparticle surface, PEG can also lower cellular internalization efficiency and binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics. Using ICP-MS analysis of blood, urine, and several organs, we show in this article that glutathione-coated gold nanoparticles (1.2 nm ± 0.9 nm) cause no morbidity at any concentration up to and including 60 μM and target primary organs although providing gradual dissipation and clearance over time. This study suggests that glutathione may be an attractive alternative to PEG in the design of gold nanoparticle therapeutics.
FROM THE CLINICAL EDITOR - This study describes the utility and toxicity of glutathione coated gold nanoparticles in comparison to PEGylated counterparts that are commonly used to increase "Stealth" properties and lower cytotoxicity. Too much PEG on the NPs can lead to lower cellular internalization efficiency and less efficient binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics.
Copyright © 2013 Elsevier Inc. All rights reserved.
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9 MeSH Terms
Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.
Bhatnagar P, Purvis S, Barron-Casella E, DeBaun MR, Casella JF, Arking DE, Keefer JR
(2011) J Hum Genet 56: 316-23
MeSH Terms: African Continental Ancestry Group, Anemia, Sickle Cell, Bayes Theorem, Carrier Proteins, Chromosomes, Human, Pair 17, Cohort Studies, Erythrocyte Count, Erythrocytes, Fetal Hemoglobin, Genome-Wide Association Study, Genotype, Glucagon-Like Peptide-1 Receptor, Haplotypes, Humans, Male, Nuclear Proteins, Polymorphism, Single Nucleotide, Receptors, Glucagon, Repressor Proteins
Show Abstract · Added November 27, 2013
Fetal hemoglobin (HbF) level has emerged as an important prognostic factor in sickle-cell disease (SCD) and can be measured by the proportion of HbF-containing erythrocytes (F-cells). Recently, BCL11A (zinc-finger protein) was identified as a regulator of HbF, and the strongest association signals were observed either directly for rs766432 or for correlated single-nucleotide polymorphisms (SNPs). To identify additional independently associated genetic variants, we performed a genome-wide association study (GWAS) on the proportion of F-cells in individuals of African ancestry with SCD from the Silent Infarct Transfusion (SIT) Trial cohort. Our study not only confirms the association of rs766432 (P-value <3.32 × 10(-13)), but also identifies an independent novel intronic SNP, rs7606173, associated with F-cells (P-value <1.81 × 10(-15)). The F-cell variances explained independently by these two SNPs are ∼13% (rs7606173) and ∼11% (rs766432), whereas, together they explain ∼16%. Additionally, in men, we identify a novel locus on chromosome 17, glucagon-like peptide-2 receptor (GLP2R), associated with F-cell regulation (rs12103880; P-value <3.41 × 10(-8)). GLP2R encodes a G protein-coupled receptor and involved in proliferative and anti-apoptotic cellular responses. These findings highlight the importance of denser genetic screens and suggest further exploration of the BCL11A and GLP2R loci to gain additional insight into HbF/F-cell regulation.
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19 MeSH Terms
Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.
Socolovsky M, Nam H, Fleming MD, Haase VH, Brugnara C, Lodish HF
(2001) Blood 98: 3261-73
MeSH Terms: Anemia, Animals, Apoptosis, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Erythroblasts, Erythrocyte Count, Erythroid Precursor Cells, Erythropoiesis, Erythropoietin, Fetal Diseases, Genotype, Hematocrit, Mice, Mice, Inbred C57BL, Milk Proteins, Polymerase Chain Reaction, Proto-Oncogene Proteins c-bcl-2, Receptors, Erythropoietin, STAT5 Transcription Factor, Spleen, Stress, Physiological, Trans-Activators, bcl-X Protein
Show Abstract · Added August 19, 2013
Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a(-/-)5b(-/-) mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a(-/-)5b(-/-) mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a(-/-)5b(-/-) mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a(-/-)5b(-/-) hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-x(L) and increased apoptosis in Stat5a(-/-)5b(-/-) early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.
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25 MeSH Terms
Impaired biological activity of erythropoietin by cyanate carbamylation.
Mun KC, Golper TA
(2000) Blood Purif 18: 13-7
MeSH Terms: Animals, Body Weight, Carbamates, Cyanates, Erythrocyte Count, Erythropoietin, Hematocrit, Hemoglobins, Male, Rats, Rats, Sprague-Dawley, Sodium Chloride, Time Factors
Show Abstract · Added August 7, 2015
AIMS - During advanced renal failure, particularly in patients with end-stage renal disease (ESRD), proteins are carbamylated as a result of a reaction with cyanate. Some or all of the cyanate is derived from urea. If the carbamylation of proteins adversely alters their biologic activities, then urea must be viewed as an uremic toxin, rather than a surrogate. Therefore, we studied the effect of cyanate carbamylation on the erythropoietic activity of erythropoietin (EPO) in a rodent model.
METHODS - EPO was carbamylated by incubation with cyanate at 37 degrees C. The extent of carbamylation was monitored using trinitrobenzenesulfonic acid. In Sprague-Dawley rats the erythrocyte count, hemoglobin concentration, and hematocrit were measured after the twice-weekly subcutaneous injection of either EPO or carbamylated EPO for 3 weeks. Two additional control groups received physiologic saline or 0.2 ml of 1 M cyanate.
RESULTS - The level of carbamylated EPO was increased as the time of exposure to cyanate increased from 1 to 6 h, and as the cyanate concentration increased from 8 to 2,000 mM. EPO injections caused significantly large increases in all erythropoietic measures. Physiologic saline or 1 M cyanate-injected controls and the carbamylated EPO-injected animals demonstrated no change from baseline in erythropoietic parameters.
CONCLUSION - These results support that EPO exposed to high levels of cyanate in vitro demonstrates diminished biologic activity in healthy Sprague-Dawley rats. This effect may be manifested by the carbamylation of EPO by the cyanate. Should this occur in ESRD patients, it may contribute to the suboptimal erythropoietic response to EPO therapy associated with high urea levels, especially related to inadequate dialysis. Targeting dialysis doses specifically to urea concentrations may be more important than previously considered.
Copyright 2000 S. Karger AG, Basel
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13 MeSH Terms
Evaluation of complete blood count results from a new, on-site hemocytometer compared with a laboratory-based hemocytometer.
Despotis GJ, Alsoufiev A, Hogue CW, Zoys TN, Goodnough LT, Santoro SA, Kater KM, Barnes P, Lappas DG
(1996) Crit Care Med 24: 1163-7
MeSH Terms: Erythrocyte Count, Erythrocyte Indices, Extracorporeal Circulation, Hematocrit, Hematologic Tests, Hemoglobinometry, Humans, Intensive Care Units, Laboratories, Hospital, Leukocyte Count, Platelet Count, Prospective Studies
Show Abstract · Added March 5, 2014
OBJECTIVE - To compare point-of-care results obtained from an on-site hemocytometer with values provided by an institutional laboratory instrument.
DESIGN - A prospective laboratory evaluation.
SETTING - The central laboratory and cardiac surgical intensive care unit of a university-affiliated tertiary care center.
PATIENTS - Normal range comparison was performed using blood specimens routinely obtained from 48 hospitalized patients for complete blood count analysis. The second evaluation was performed on blood specimens routinely obtained (in the intensive care unit) after cardiac surgery involving extracorporeal circulation in a series of 187 consecutive patients.
MEASUREMENTS AND MAIN RESULTS - Hemoglobin concentration, platelet count, mean corpuscular volume, mean platelet volume, and red and white blood cell counts were measured with both on-site (MD 16, Coulter Electronics, Hialeah, FL) and laboratory (STKS, Coulter Electronics) instruments. Hematocrit and red cell distribution width were calculated using measured variables. Blood specimens were obtained from two distinct patients series. To evaluate measurement values within the normal range, a series of 48 routinely obtained blood specimens for complete blood count analysis in our institutional laboratory were utilized for concurrent analysis with the on-site hemocytometer. To evaluate measurement values out of the normal range, a second comparison involved measurements performed on blood specimens obtained in the cardiac surgical intensive care unit for complete blood count analysis. Linear regression demonstrated good correlations between on-site and laboratory hemoglobin concentration (r2 = .97), hematocrit (r2 = .95), platelet count (r2 = .97), mean corpuscular volume (r2 = .91), red cell distribution width (r2 = .80), and red (r2 = .95) and white (r2 = .96) blood cell count results. A marginal correlation was observed between mean platelet volume values (r2 = .47). Bias analysis (mean +/- 2 SD) demonstrated similar measurements between on-site and laboratory hemoglobin concentration, hematocrit, platelet count, red blood cell count, white blood cell count, mean platelet volume, mean corpuscular volume, and red cell distribution width.
CONCLUSIONS - On-site hemoglobin concentration, hematocrit, white blood cell count, red blood cell count, red cell distribution width, and platelet count values compare well with those results obtained from the laboratory. The MD 16 hemocytometer (Coulter Electronics) provides on-site hematologic results that can provide an accurate and rapid quantitative assessment of platelets, and red and white blood cells. Rapid access to information obtained from this type of system may be clinically useful, especially in critically ill patients.
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12 MeSH Terms
Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant women.
Slunga-Tallberg A, el-Rifai W, Keinänen M, Ylinen K, Kurki T, Klinger K, Ylikorkala O, Knuutila S
(1995) Hum Genet 96: 53-7
MeSH Terms: Cell Nucleus, Erythrocyte Count, Erythrocytes, Female, Fetal Blood, Humans, Immunophenotyping, In Situ Hybridization, Fluorescence, Male, Pregnancy
Show Abstract · Added March 5, 2014
We studied the origin of nucleated red blood cells (NRBC) in peripheral venous blood samples from 40 pregnant women carrying a male fetus, using a technique that allows direct chromosomal analysis by in situ hybridisation on immunologically and morphologically classified cells. Samples from ten nulligravid women were studied as controls. NRBC were enriched by negative magnetic activated cell sorting (miniMACS) using anti-CD45 monoclonal antibody. NRBC were detected by alkaline phosphatase anti-alkaline phosphatase immunostaining using a monoclonal anti-glycophorin A antibody. The origin of the NRBC was determined by fluorescence in situ hybridisation using X and Y specific probes. NRBC were found in 37 of the 40 pregnant women at a range of 1 to 230 per 20 ml of venous blood and in 6 of the 10 controls at a range of 1 to 3 per 20 ml of venous blood. All NRBC detected in the pregnant women were evidently of maternal origin, and in the pregnant women the number of NRBC was significantly higher (P < 0.05) than in the controls. Pregnancy per se seems to induce the appearance of maternal NRBC in the circulation, and it cannot therefore be assumed that NRBC isolated from the maternal blood are of fetal origin on the basis of morphology alone. Discrimination of fetal NRBC must occur for prenatal diagnosis of fetal genetic disorders.
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10 MeSH Terms